Trimetazidine increases [3H]glucose uptake in rat brain

Trimetazidine, a clinically effective antianginal agent with no negative inotropic or vascular properties, acts by optimizing cardiac energy metabolism through inhibition of free fatty acid oxidation, shifting substrate utilization from fatty acids to glucose. Up to now there has been no study associating trimetazidine's effect on metabolic processes with glucose utilization in the mammalian brain. The objective of the present study was to determine if trimetazidine altered [(3)H]glucose uptake in rat brain. Adult male Wistar rats were administered trimetazidine (Metazydyna, Polfa) either as a single dose (10.0 mg/kg po) or for 14 consecutive days (5.0 mg/kg po per day) or vehicle saline (2.0 ml/kg po). Sixty minutes after the single dose or 14th dose of trimetazidine, and 15 min before experiment termination and brain dissection, 6-[(3)H]D-glucose (500 Ci/kg ip; Amersham) was administered. Using liquid scintillation counting, trimetazidine, either in a single or multiple dose regimen, was found to increase [(3)H]glucose uptake (DPM/100 mg of wet tissue) in all dissected regions of the brain (i.e., striatum, hippocampus, frontal cortex, thalamus with hypothalamus, pons with medulla oblongata, and cerebellum). Therefore, central effects need to be taken into consideration as possibly adding to known beneficial cardiac effects of trimetazidine.     

Effects of I.C.V. administration of ethylcholine aziridinium (AF64A) on the central glutamatergic nervous systems in rats

Changes in glutamatergic nervous activities following intracerebroventricular (icv) administration of ethylcholine aziridinium (AF64A) were studied in rats. The levels of total glutamate, those of glutamate in cerebrospinal fluid (CSF) and in extracellular fluid (ECF) of striatum, the activities of glutamine synthetase (GS), glutaminase and glutamate dehydrogenase (GDH) and the specific binding sites of [³H]MK801 in striatum, hippocampus and frontal cortex were assessed a week after the infusion of AF64A (3 nmol) into lateral ventricle. The levels of total glutamate were significantly decreased in striatum, hippocampus and frontal cortex after AF64A treatment. Although the levels of glutamate in CSF weren't changed after AF64A treatment, the levels of glutamate in ECF of striatum were significantly decreased (62.6%). GS activities in striatum were significantly decreased. But, glutaminase activities in striatum were significantly increased. However, the activities of GS and glutaminase in frontal cortex and hippocampus weren't changed. Although GDH activities in frontal cortex were significantly decreased, those in striatum and hippocampus weren't altered. The striatal densities of [³H]MK 801 binding sites were increased without changes in its affinity. Also, the specific binding sites of [³H]MK801 were increased in frontal cortex but not in hippocampus. These results indicate that the glutamatergic nervous activities were altered with the infusion of AF64A into lateral ventricle. Furthermore, it suggest that the decreased levels of glutamate after AF64A treatment may affect the change in the other parameters of glutamatergic neuronal activities.     

In vivo [3H]spiperone binding to the rat hippocampal formation: Involvement of dopamine receptors

The existence of DA receptors in the rat hippocampus was demonstrated with an in vivo [³H]spiperone radio-receptor assay. Kinetic studies revealed that maximum binding of [³H]spiperone in hippocampus was much smaller than in striatum and frontal cortex but much higher than in cerebellum. In inhibition studies of [³H]spiperone binding, all neuroleptics tested were active in hippocampus as well as in striatum. In contrast, 5HT antagonists were definetely less potent in these two brain regions than in frontal cortex. Finally, even when 5HT receptors were blocked, dipropyl-ATN and haloperidol remained fully effective in hippocampus, striatum, but also in frontal cortex although to a lesser degree. From these results it was concluded that [³H]spiperone binds mainly to DA receptors in hippocampus as well as in striamtum, whereas both 5HT and DA receptors are present in frontal cortex.     

Down-regulation of central receptors for thyrotropin-releasing hormone in kappa opiate agonist-induced abstinence in the rat.

The effect of U-50,488H, a selective kappa opiate agonist, on tolerance-dependence and abstinence on the TRH receptors of the spinal cord and discrete regions of the brain of male Sprague-Dawley rats was determined. Rats were injected intraperitoneally twice daily with 25 mg/kg of U-50,488H for 4 days. Rats serving as controls were injected with the vehicle. On day 5, rats which were labeled as tolerant to U-50,488H were injected with U-50,488H (25 mg/kg) and sacrificed 1 hr later, whereas those labeled as abstinent were sacrificed without any injection. The above procedure has been previously shown to produce a high degree of tolerance to the analgesic and hypothermic effects of U-50,488H. The spinal cord and regions of the brain (hippocampus, cortex, midbrain, hypothalamus, corpus striatum, pons and medulla, and amygdala) were isolated for binding studies. The ligand [3H]MeTRH was used for TRH receptors. The binding constants, Bmax and Kd values, of [3H]MeTRH to bind to membranes prepared from various regions of the brain and spinal cord of rats tolerant-dependent on U-50,488H were unaffected. However, in rats abstinent to U-50,488H, the binding of [3H]MeTRH to membranes of the hypothalamus, and pons and medulla, was decreased. The decreased binding of [3H]MeTRH to hypothalamic membranes was due to changes in Bmax value, while in pons and medulla it was due to an increase in the Kd value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Colchicine administered into the area of the nucleus basalis decreases cortical nicotinic cholinergic receptors labelled by [3H]-acetylcholine

Lesions in the nucleus basalis in the rat are known to decrease presynaptic markers for acetylcholine, including levels of cholineacetyltransferase (CHAT), high affinity uptake of choline and levels of acetylcholinesterase. Effects of lesions of the nucleus basalis on populations of nicotinic and muscarinic receptors are less well understood. After bilateral injection of the neurotoxic agent, colchicine into the nucleus basalis in the rat, levels of CHAT in the cerebral cortex were reduced 44%. Muscarinic cholinergic [( 3H]QNB) and dopaminergic [( 3H]spiroperidol) binding was not changed in the cortex, hippocampus or striatum. However, significant decreases in nicotinic binding sites, labelled by [( 3H]acetylcholine), were observed in the frontal cortex of nucleus basalis treated animals; scatchard plot analysis indicated a significant decrease in the number, but not affinity, of nicotinic binding sites. Colchicine injected into the nucleus basalis had no effect on the binding of [3H]acetylcholine in the hippocampus, but decreased binding of [3H]acetylcholine in the striatum. Subsequent experiments, in which colchicine was administered into the striatum at a site above the nucleus basalis had no significant effect on nicotinic binding in the striatum or frontal cortex. These results support the hypothesis that degeneration of the nucleus-basalis-cortical cholinergic pathway results in a loss of presynaptic nicotinic binding sites in the cortex as well as in the striatum (through transsynaptic degeneration of the cortico-striatal pathway).     

Alterations in hippocampal function following repeated exposure to the amphetamine derivative methylenedioxymethamphetamine (“Ecstasy”)

The effect of the psychomotor stimulant, 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”), upon integrated cerebral function was measured in rats using the quantitative [¹⁴C]deoxyglucose autoradiographic technique. Animals were injected with MDMA (20 mg/kg sc) twice daily for 4 days. Fourteen days after the final administration, [³H]-paroxetine binding to 5HT uptake sites was reduced by 89% in membranes prepared from tissue samples of frontal cortex. In the same rats [³H]-paroxetine binding autoradiography revealed heterogeneity in the regional distribution of 5-HT uptake site depletion within neocortex (0–92%) and hippocampus (30–95%). Despite these profound reductions in 5-HT uptake sites no significant alterations were found in glucose utilisation in any area of neocortex examined. However, significant increases in glucose use were found in subregions of the hippocampus, most notably within the pyramidal cell layer of CA2 and CA3 (25–35%). This study provides direct evidence that the loss of 5-HT innervation caused by exposure to MDMA results in lasting functional changes in hippocampus.     

Effect of prenatal manganese intoxication on [3H]glucose uptake in the brain of rats lesioned as neonates with 6-hydroxydopamine

In the present study we examined the effects of prenatal manganese (Mn) intoxication on [³H]glucose uptake in the brain of rats lesioned as neonates with 6-hydroxydopamine (6-OHDA). MnCl₂ ? 4H2O (10,000 ppm) was added to the drinking water of pregnant Wistar rats for the duration of pregnancy. On the day of parturition, Mn was discontinued as an additive to the drinking water. The control group consisted of rats that consumed water without Mn. Three days after birth, rats in both groups (control and Mn) were pretreated with desipramine hydrochloride (20 mg/kg) and pargyline hydrochloride (50 mg/kg) and injected bilaterally icv with one of three doses of 6-OHDAhydrobromide (15 μg, 30 μg or 67 μg base form in saline on each side) or with saline (control). 6-[³H]-Dglucose (500 μCi/kg, ip) was administered to male offspring in adulthood; after 15 min, brain specimens were taken (frontal cortex, hippocampus, striatum, thalamus with hypothalamus, pons and cerebellum) for determination of radioactivity in a liquid scintillation counter. Low dose 6-OHDA (15 μg icv) increased [³H]glucose uptake in all brain regions (p < 0.05) in both control and Mnintoxicated animals. In rats lesioned with a moderate dose of 6-OHDA(30 μg icv), [3H]glucose uptake was unaltered in both control and Mn-exposed rats. High dose 6-OHDA(67 μg icv) reduced [³H]glucose uptake in all brain regions of Mn-exposed rats (except for cerebellum) compared with the saline group (all, p < 0.05). There was no change in regional brain uptake of [³H]glucose in control rats. In conclusion, this study shows that mild neuronal insult (15 μg icv 6-OHDA) increased glucose uptake in the brain while severe damage (concomitant 60 μg icv 6-OHDA and Mn treatment) significantly diminished this process.     

Handling habituation and chlordiazepoxide have different effects on GABA and 5-HT function in the frontal cortex and hippocampus.

In slices of frontal cortex and hippocampus from rats that had been habituated to handling for 21 days, there was significantly less 20 mM K(+)-evoked release of [14C]GABA ([14C]gamma-aminobutyric acid) compared with rats naive to handling. Handling for 21 days also significantly increased the uptake of [14C]GABA into frontal cortex and hippocampus. The change in uptake in the hippocampus was independent of any changes in release and could account for the apparent change in evoked release; in the cortex there were no independent changes in uptake and K(+)-evoked release. When the changes in uptake were taken into account, there were no independent changes in basal release of GABA in either region. HPLC analysis showed the change in uptake was not due to differences between the groups in endogenous GABA concentrations. Acute administration of chlordiazepoxide (CDP 7.5 mg/kg i.p.) to handling naive rats also significantly reduced K(+)-evoked [14C]GABA release from the cortex and hippocampus, but basal release and GABA uptake were unchanged. Neither handling nor CDP administration significantly changed the K(+)-evoked [3H]5-HT release, however, the uptake of 5-HT and its basal release in both regions were both significantly and independently increased in animals habituated to handling, compared with handling naive animals. In the hippocampus, the endogenous 5-HT concentrations were significantly lower in the rats that had received 21 days of handling, compared with handling naive rats. In the cortex the endogenous 5-hydroxyindoleacetic acid concentrations were significantly lower in the group that had been handled for 21 days. Thus both the GABA and 5-HT systems were responsive to handling habituation.     

Acute exposure to noise affects sodium-dependent high-affinity choline uptake in the central nervous system of the rat

Rats were acutely (45 min) exposed to white noise at intensity of either 70 or 100 dB. Sodium-dependent high-affinity choline uptake was determined in the striatum, frontal cortex, hypothalamus, and hippocampus immediately after exposure. The effects of noise on choline uptake varied according to the intensity of the noise and the brain area studied. Exposure to noise of 70 dB significantly increased the choline uptake in the frontal cortex, hypothalamus, and hippocampus as compared to the uptake of sham-exposed rats, whereas decreased choline uptake in the frontal cortex and hippocampus was observed acute exposure to noise of 100 dB. No significant effect on choline uptake in the striatum was seen after exposure to noise of either intensity. In addition, pretreatment of the rats with the narcotic antagonist naltrexone (1 mg/kg, IP) before noise exposure blocked the effects of noise on choline uptake in the central nervous system. Changes in cholinergic activity in the central nervous system could be a response to the stress effect of noise and may be mediated by endogenous opioids.     

Changes in multiple opioid receptors in regions of the brain in rats treated chronically with thyroxine

The effect of the administration of thyroxine (T4) (1 mg/kg, s.c.), to male Sprague-Dawley rats on alternate days for 18 days, on the binding of opioid ligands, [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO, mu receptors), [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta receptors) and [3H]ethylketocyclazocine (EKC, kappa receptors) to membranes of regions of the brain was determined. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased colonic temperature and increased systolic blood pressure and heart rate, in comparison to vehicle-injected rats. The administration of thyroxine also increased the serum concentration of triiodothyronine (total T3) and thyroxine, when compared to vehicle-injected rats. The binding of [3H]DAGO to membranes of the striatum of rats treated with thyroxine was greater than in vehicle-treated rats; however, the binding to membranes of pons and medulla, amygdala, hypothalamus, midbrain and cortex in the two treatment groups did not differ. The increased binding of [3H]DAGO in rats treated with thyroxine was due to an increase in the Bmax value. The binding of [3H]DSTLE in the midbrain, hypothalamus, pons and medulla and striatum of rat treated with thyroxine and vehicle-injected rats did not differ but it was significantly less in the amygdala of rats injected with thyroxine than in vehicle-injected rats. The decreased binding in the amygdala was due to changes in the Kd value of [3H]DSTLE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of N-methyl-d-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats

We studied the aggressive behaviour induced by repeated treatment with apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats. The first signs of defensive aggressiveness appeared on the third day of apomorphine treatment and were generally seen on the 7th day. Aggressiveness induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg i.p., dizocilpine even accelerated the appearance of apomorphine-induced aggressive behaviour, which manifested on the 3rd day in all rats. In a separate study, a 7-day treatment with dizocilpine (0.25–1 mg/kg i.p.) of rats, sensitized by a prior 10-day apomorphine treatment, did not reverse the established aggressive behaviour. The coadministration of apomorphine and cholecystokinin (CCK)-A or -B antagonists, devazepide or L-365,260 (0.01–2.5 mg/kg i.p.) respectively, neither affected development of apomorphine-induced aggressive behaviour nor intensity of aggressiveness in the sensitized rats.In binding studies neither density nor affinity of striatal dopamine D₂ receptors was changed by acute or chronic apomorphine treatment. The number of [³H]pCCK-8 binding sites in the frontal cortex increased already after a single injection of apomorphine. After 10-day administration of apomorphine, a significant upregulation of [³H]pCCK-8 binding sites occurred in the frontal cortex and striatum, but a downregulation was observed in the hippocampus. A challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day of experiment, normalized the upregulated CCK receptors in the frontal cortex and striatum. Acute apomorphine did not change [³H]-MK-801 binding in the rat brain. However, in rats treated for 10 days with apomorphine, the number of NMDA-gated channels in open state was increased in the frontal cortex and hippocampus. In these rats, a challenge dose of apomorphine (0.5 mg/kg s.c.) normalized also the in reased number of [³H]-MK-801 binding sites in the frontal cortex.In conclusion, repeated treatment with apomorphine seems to modify the function of dopamine D₂ receptors without affecting their number or affinity. The increased number of NMDA-gated channels in open state appears to be related to this alteration of dopamine D₂ receptors. The increased density of [³H]pCCK-8 binding sites in the frontal cortex may reflect anxiety and fear due to chronic exposure of rats to apomorphine.     

Acute stress and GABAergic function in the rat brain.

1. The function of the gamma-aminobutyric acid (GABA)-ergic system in certain areas of the rat brain was investigated after acute (5 min) exposure to immobilization stress. 2. The activities of glutamate decarboxylase and GABA-transaminase, GABA concentrations, GABA turnover in vivo and uptake of [3H]-GABA were measured. 3. After 5 min of immobilization stress, GABA concentrations and [3H]-GABA uptake were reduced, and GABA turnover stimulated in the olfactory bulbs. In contrast the uptake of [3H]-GABA was increased in the corpus striatum after 5 min of immobilization stress. 4. None of the parameters measured was significantly altered by acute immobilization stress in the frontal cortex, hippocampus or medio-basal hypothalamus. 5. These findings show that the olfactory bulbs and the corpus striatum are sensitive to the effects of acute stress. Since GABA in the olfactory bulbs is involved in the development of aggression and increased emotional state, it follows that neurochemical changes induced by acute stress might underlie some behavioural manifestations observed after stress.     

Effect of the combination of the benzodiazepine tranquilizer medazepam and the nootropic agent meclofenoxate on the activity of rat brain muscarinic receptors

1. The effect of 7-day treatment with the benzodiazepine tranquilizer medazepam (5 mg/kg), the nootropic agent meclofenoxate (100 mg/kg) and their combination in the same doses on the binding activity of muscarinic receptors in four rat brain structures (cerebral cortex, striatum, hippocampus and hypothalamus) were studied using the antagonist [3H]-1-quinuclidinyl benzylate [( 3H]-QNB) as radio-ligand. 2. Medazepam treatment caused significant decrease of muscarinic receptor binding affinity (Kd) and of the receptor binding capacity (Bmax) in the brain structures studied. The number of muscarinic binding sites was unsignificantly decreased only in the hippocampus. 3. Meclofenoxate treatment caused an increase of muscarinic receptor affinity and a decrease of the binding capacity in the cerebral cortex and hypothalamus and an increase of the binding affinity in the striatum and hippocampus. 4. The combination of medazepam and meclofenoxate caused no significant changes of both muscarinic receptor characteristics in the hippocampus and of the receptor affinity in the striatum and hypothalamus in comparison with control rats. The Bmax values were decreased in the cerebral cortex, striatum and hypothalamus when compared with control animals. The differences observed were slighter than those determined after the comparison of medazepam treated rats with control rats. 5. The results obtained afford an opportunity to suggest that the nootropic agent meclofenoxate acts to moderate the effect of the benzodiazepine tranquilizer medazepam on the activity of rat brain muscarinic receptors.     

M1 acetylcholine receptor-mediated phosphatidylinositol turnover in adult and senescent rat brain slices.

Phosphatidylinositol (PI) turnover via muscarinic acetylcholine (mACh) receptor was investigated using the cerebral cortex from adult rats. Activities in the cerebral cortex, hippocampus and striatum from senescent rats were compared with those from adult rat. Carbachol (1 mM)-stimulated [3H]IP accumulation in the presence of 10 mM LiCl was inhibited by pirenzepine more potently than by AF-DX 116. Although the displacing activity of carbachol for [3H]pirenzepine binding was decreased by 50 microM GTP gamma S, pretreatment of slices with pertussis toxin (PTX, 0.01-1.0 micrograms/ml) did not affect the carbachol-induced [3H]IP accumulation. In the slices from all 3 tissues, cerebral cortex, hippocampus and striatum, both incorporation of [3H]inositol and carbachol-stimulated [3H]IP accumulation were reduced at 28 months compared to those at 2 months. Furthermore, the Bmax values of [3H]pirenzepine binding in membranes from these three regions were diminished at the senescent stage. Taken together, the results suggest that an M1-subtype of muscarinic acetylcholine receptor could be involved in PI turnover via GTP-binding proteins insensitive to PTX. Age-related changes in M1-receptor mediated PI turnover seem to be in part due to the decreased number of M1-receptors with increasing age in the cerebral cortex, hippocampus and striatum; and some qualitative changes also seem to have occurred in the hippocampus of senescent rats in the mACh receptor-PI turnover system.     

Amphetamine-induced effects on neuropeptide Y in the rat brain

Repeated (+)-amphetamine sulfate (AMPH) administration (5 mg/kg sc twice daily for 6 days and once on day 7) markedly and reversibly decreased (until 96 h after the final dose) neuropeptide Y-like immunoreactivity (NPY-LI) in the rat striatum (caudate-putamen) and nucleus accumbens, and had no effect on NPY-LI in the hippocampus. No significant alterations were detected in the hybridization signal of NPY mRNA4 and 24 h after the end of AMPH treatment. A single dose of AMPH (5 mg/kg sc) administered to rats 4 and 24 h prior to sacrifice had no effect on NPY-LI in the brain structures studied. Moreover, AMPH injected 8 days after the last dose of repeated AMPH administration did not change NPY-LI up to 72 h. The minimal dose of haloperidol, the strong mixed dopaminergic D2/D1 receptor antagonist, (0.75 mg/kg injected ip 30 min before each of the multiple AMPH administrations) that was sufficient to completely block stereotypy and hyperlocomotion elicited by multiple AMPH administrations enhanced the AMPH-induced decrease in the striatal and accumbens NPY-LI. Our results suggest that NPY neurons in the striatum, nucleus accumbens and hippocampus are not directly involved in the acute behavioral response to AMPH (stereotypy and hyperlocomotion) as well as in the initiation and expression of AMPH-induced behavioral sensitization.     

Changes in 5-HT1 receptors in different brain structures of rats with isolation syndrome

1. Prolonged (3 month) individual housing of Wistar rats produced aggressive muricidal behavior in 28% of the animals. 2. Binding studies with [3H]5-HT showed that the affinity (Kd) of 5-HT1 receptors in the frontal cortex, striatum, hippocampus and hypothalamus of isolated aggressive rats was significantly decreased as compared to that in grouped rats. 3. The affinity of 5-HT1 receptors was also significantly decreased in the striatum, hippocampus and hypothalamus of isolated nonaggressive rats. 4. The number (Bmax) of 5-HT1 receptors was significantly decreased in the hippocampus and hypothalamus of isolated aggressive rats and in isolated nonaggressive rats it was decreased only in the hypothalamus. 5. The data suggest that aggressive muricidal behavior in rats with syndrome of social isolation is connected with the decreased activity of brain 5-HT1 receptors.     

Changes in GABAergic function after chronic chemical stress.

1. The function of the gamma-aminobutyric acid (GABA)-ergic system in certain areas of the rat brain was investigated after chronic chemical stress (exposure to either vapours 30 sec/day for 20 days). 2. GABA concentration, [3h] -GABA uptake and the activity of the synthesis enzyme glutamate decarboxylase (GAD) were measured. 3. Chronic stress: (a) reduced neuronal uptake of [3H] -GABA in the frontal cerebral cortex (43%) and increased non-neuronal uptake of [3H] -GABA in the hypothalamus (62%); (b) enhanced the activity of GAD (under subsaturating substrate concentration) in the frontal cortex (91%) and in the corpus striatum (69%); (c) did not modify GABA endogenous concentration; (d) did not affect the animals' body weight increase or produce any signs of toxicity. 4. The stimulation of GAD and reduction of [3H] -GABA neuronal uptake in the frontal cortex might suggest the stimulation of GABAergic neurotransmission induced by chronic stress in this area of the rat brain. Together with previous findings the frontal cortex would appear to be a key area in chronic stress processing.     

Triethyllead-induced peroxidative damage in various regions of the rat brain

Adult male Fisher 344 rats (8-10 wk old) were dosed ip with 1.75 mg/kg body weight of triethyllead chloride (TEL) for 5 consecutive days. Rats were sacrificed 1, 7, or 21 d after the last injection. The rate of lipid peroxidation was significantly elevated in frontal cortex at all three time points assayed (1, 7, or 21 d). However, hippocampal and cerebellar membranes showed no changes in peroxidative capacity at these time points. In order to determine whether cortical membrane damage was reflected in alteration of a restricted protein population, a series of high-affinity receptor binding sites was determined in cortical membranes derived from treated rats 7 d after the last injection of triethyllead. The rate of lipid peroxidation was significantly increased in the frontal cortex of triethyllead treated rats; however, no changes in the binding of [3H]spiroperidol, [3H]quinuclidinyl benzilate, and [3H]benzodiazepine were seen in animals exposed to triethyllead. The cortical wet weight, protein content, and cell number were also unchanged by TEL treatment, reflecting an absence of gross damage.     

Effect of ovariectomy and estrogen on [3H]imipramine binding to different regions of rat brain

In rats, 35 days after ovariectomy, the number of [3H]imipramine binding sites increased more than 200% in striatum, hippocampus and hypothalamus but it did not change in cerebral cortex and brain-stem. Estradiol-17 beta acting in vitro inhibited [3H]imipramine binding in control membranes of striatum, hippocampus and hypothalamus, but not in the same regions from ovariectomized rats.     

Effect of oxotremorine on endogenous acetylcholine and on uptake and biotransformation of radioactive choline in discrete regions of mouse brain in vivo.

Oxotremorine (1 mg/kg) was injected intraperitoneally 15 min before an intravenous dose of 15 nmoles of tritium-labelled choline ([³H]choline). The animals were sacrificed 1 or 5 min later by dislocation of the spine. Hypothermia was prevented by a heating lamp. The brains were rapidly dissected into six well-defined regions (cerebellum, medulla oblongata, midbrain, striatum, hippocampus and cortex). Endogenous acetylcholine was significantly (P < 0.01) increased in the striatum (+87%), hippocampus (+49%) and cortex (+115%) but unchanged in the cerebellum, medulla oblongata and midbrain. Pretreatment with methylatropine (5 mg/kg) and with atropine (5 mg/kg) partly counteracted the increase of endogenous acetylcholine in the cortex, and atropine also had the same effect in the striatum. The biosynthesis of [³H]acetylcholine at 1 and 5 min was decreased in all regions except the striatum. This was prevented by pretreatment with atropine (5 mg/kg); methylatropine (5 mg/kg) was considerably less effective. In the striatum the formation of [³H]acetylcholine was increased (+74–101%) after administration of oxotremorine. The increase was not antagonized by pretreatment with atropine (5 mg/kg) or methylatropine (5 mg/kg). Oxotremorine produced a marked decrease in the specific radioactivities of acetylcholine in the hippocampus and cortex but not in the striatum.